ERCC1 AND BETA-TUBULIN III IN ADVANCED NSCLC PATIENTS TREATED WITH CISPLATIN-VINORELBINE
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2012
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LIPPINCOTT WILLIAMS & WILKINS
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JOURNAL OF THORACIC ONCOLOGY, v.7, n.6, suppl.S, p.S33-S34, 2012
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Background: Platinum-containing chemotherapy remains as the standard treatment in advanced/metastatic non-small-cell lung cancer (NSC LC) patients (pts). Increased ERCC 1 expression has been associated with resistance to platinum-based therapies, and beta-tubulin III (TUBB 3) was shown to be involved in resistance to antimicrotubule agents. Here we studied these tumor markers in NSC LC pts treated with cisplatin-vinorelbine and correlated their expression with survival. Methods: It is a retrospective study on pts diagnosed with advanced/metastatic NSC LC (TNM 6th ed), consecutively identified. All pts were treated with cisplatin 80 mg/m2 d1 and vinorelbine 30 mg/m2 d1, d8, d15, every 21 days, 4–6 cycles, in our Institution, between Sep/2002 and Oct/2008. ERCC 1 (clone 8F1) and TUBB 3 (clone TUJ1) expression were evaluated by immunohistochemistry, and biomarker expression was considered as high when more than 10% of tumor cells presented moderate to strong staining, nuclear or cytoplasmic, respectively. Overall survival (OS) was estimated by the Kaplan-Meier method and curves were compared with log-rank. Results: 142 pts were studied; median age 63 y (34-87), 67% male and 86% current smokers. Adenocarcinoma (ADC, 58 pts, 43%), followed by squamous cell carcinoma (SCC , 50 pts, 37%) were the most frequent histologic types. 100 pts (71%) were staged as IV and 34 pts (24%) as IIIB. The median number of cycles was 4 (1-7). Median OS was 7.9 mo. Overall, high ERCC 1 expression was observed in 61/104 pts (59%) and high TUBB 3 expression in 55/109 pts (51%). According to histologic types, low ERCC 1 expression was observed in 7/42 SCC pts (16%) and in 35/63 ADC pts (56%) (p=0.0004). Among ADC pts, 1-y OS rate was 28% and 47% in pts which tumors presented with high and low ERCC 1 expression, respectively (HR 1.57, 95% CI 0.9-2.7, p=0.08). TUBB 3 expression neither presented any difference between SCC and ADC types, nor any prognostic impact in terms of OS. Conclusions: Low ERCC 1 expression was observed more frequently in pts with advanced lung ADC and it was a favorable prognostic factor in ADC pts treated with cisplatin-vinorelbine.